Tumorigenesis is an evolutionary process that selects for genetic and epigenetic changes, allowing evasion of anti-proliferative and cell death inducing mechanisms that normally limit clonal expansion of somatic cells. Lowe et al., Nature, 432, 307-315 (2004).
It has been hypothesized that DNA damage checkpoints might become activated in the early stages of tumorigenesis, leading to cell-cycle blockade or apoptosis, either of which might constrain tumor progression. The ATM-Chk2 kinase pathway has been implicated in this process. As such, members of that pathway, including Chk2, are thought to play a role in tumorigenesis. Thus, modulators of members of the ATM-Chk2 pathway may be implicated as anticancer agents, and their use, either alone or in combination with other anticancer agents, may provide new strategies for treatment or prevention of cancer, and other diseases, disorders, and symptoms thereof where apoptotic cell death is associated.